Many drugs are mixed with a diluent before being delivered intravenously to a patient. The diluent may be, for example, a dextrose solution, a saline solution or even water. Many such drugs are supplied in powder form and packaged in glass vials. Other drugs, such as some used in chemotherapy, are packaged in glass vials in a liquid state.
Powdered drugs may be reconstituted in a well-known manner, utilizing a syringe which is used to inject liquid into the vial for mixing, the syringe eventually withdrawing the mixed solution from the vial. When a drug must be diluted before delivery to a patient, the drug is often injected into a container of diluent, where the container may be connected to an administration set for delivery to a patient. More specifically, the diluent is often packaged in glass bottles, or flexible plastic containers such as are sold under the names MINI-BAG.TM. and VIAFLEX.RTM. by Travenol Laboratories, Inc. of Deerfield, Ill. These containers have administration ports for connection to an administration set which delivers the container contents from the container to the patient. The drug is typically added to the container through an injection site on the container.
Drugs may be packaged separately from the diluent for various reasons. One of the most important reasons is that some drugs do not retain their efficacy when mixed with a diluent and thus cannot be stored for any substantial period of time. In some instances the drug and diluent will not stay mixed for a significant length of time. Also, drugs are often packaged separately from the diluent because many firms which manufacture drugs are not engaged in the business of providing medical fluids in containers for intravenous delivery.
Therefore, a doctor, nurse, pharmacist or other medical personnel must mix the drug and diluent. This presents a number of problems. The reconstitution procedure is time consuming. The operator must provide the proper diluent and a syringe before beginning. Often the powdered drug is "caked" at the bottom of the vial. Thus, when liquid is injected into the vial from a syringe, the surface area of contact between the liquid and the powdered drug may be quite small initially, thus making the mixing procedure even more time consuming. Because of the limited vial volume, the increasing drug concentration in the diluent makes it harder to finish the reconstitution process. The operator may attempt to solve this by repeatedly injecting solution into the vial, mixing and withdrawing the solution but this makes necessary additional injections and movement of the syringe which increase the likelihood of contamination. Also, it is sometimes difficult to get all of the drug and/or liquid out of the vial, thus increasing the time required to perform the reconstitution procedure.
The reconstitution procedure should be performed under preferably sterile conditions. In addition to such a requirement making the operator justifiably more cautious and consuming more time, sterile conditions are often hard to maintain. In some instances, a laminar flow hood may be required under which the reconstitution procedure is performed.
Some drugs such as, for example, some chemotherapy drugs, are toxic. Exposure of the operator to the drugs during reconstitution may be dangerous, especially if the operator works with such drugs on a daily basis and is repeatedly exposed to them.
A further problem is that the reconstitution provides a source of confusion as to which container contains which drug, because the diluent container must be marked with the drug with which it has been injected or at least the name of the patient to whom it should be delivered.
It can be seen that a closed system for separate storage of a drug and diluent would be most beneficial. Certain facts have until recently prohibited such a closed system on a commercially feasible, reasonably inexpensive basis, however. One factor which has made difficult the manufacture of a closed system having separate, selectively communicating compartments for a drug and a diluent has been the sterilization procedure. As an example, in the case of diluent in a flexible plastic container, the container with the diluent therein is sterilized by steam sterilization, or autoclaving. However, the heat generated during such a sterilization procedure would destroy the efficacy of many drugs. On the other hand, other sterilization means such as the use of ethylene oxide gas may not harm the drug but may harm the diluent. A system for sterilizing a drug and diluent separately and combining the two components into a single container having separate compartments for separate storage after sterilization is shown in a U.S. patent application in the name of William Schnell, entitled "Sterilized Liquid Mixing System," U.S. patent application Ser. No. 365,940, filed Apr. 6, 1982 and assigned to the assignee of the present invention.
These considerations mandate that, absent means to protect the drug and diluent during different sterilication steps, the system be formed by combining separate drug and diluent receptacles after they have been separately sterilized. This requires the manufacture of a sterile or at least an aseptic connection between the two receptacles. Sterile connectors are known, such as shown, for example, in U.S. Pat. Nos. 4,157,723, 4,265,280 and 4,325,417, all assigned to the assignee of the present invention. The connectors disclosed therein provide highly reliable, sterile connections. They do, however, employ a separate radiant energy source to make the connection and therefore a power supply to operate the energy source.
Another requirement of such a closed system is that it should prevent water vapor transmission from the receptacle holding the diluent to the receptacle holding the powdered drug. As discussed earlier, the storage of some powdered drugs with even a small amount of liquid destroys drug efficacy. Such a closed system should also be constructed in a manner which will facilitate easy and thorough mixing of the drug and the diluent.
In U.S. Pat. Nos. 4,410,321 and 4,411,662, both assigned to the assignee of the present invention, a closed drug delivery system is disclosed, in which a drug and a diluent are separatedly stored and selectively mixed under sterile conditions. In the illustrative embodiments, a sterile coupling is utilized which includes a permanently affixed molded junction. In some instances, however, it may be desirable to avoid the use of a permanently affixed molded junction, as part of the sterile coupling. To this end, we have developed a closed drug delivery system that enjoys most of the benefits of the system disclosed in U.S Pat. Nos. 4,410,321 and 4,411,662, yet avoids the use of a permanently affixed molded junction, allows safe and easy reconstitution of a drug just prior to use, and is relatively simple in construction and easy to manufacture.